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Recommendations for Evaluation and
Monitoring of Patients with
Joubert Syndrome and Related Disorders
Dear Healthcare Professional,
Joubert Syndrome and Related Disorders are a group of
developmental brain disorders characterized clinically
by disturbances of breathing rhythm, ataxia, oculomotor
abnormalities, developmental delays, and hypotonia.
These disorders are characterized on brain imaging by
cerebellar vermis hypoplasia and the “molar-tooth” sign
of the brainstem. From our review of clinical records
from patients in the Joubert Syndrome Foundation, we
have found many with co-existing medical conditions at a
frequency sufficient to warrant a set of guidelines
for the evaluation and monitoring of all patients with
Joubert Syndrome and Related Disorders. These
evaluations are necessary for two reasons. First is for
proper diagnosis of the child, as we find that
approximately 20% of patients display features
indicating a subtype of Joubert syndrome or a related
syndrome. Second is to try to prevent medical
complications from these associated conditions, which
through proper screening might be avoided. However,
because our total knowledge of Joubert syndrome and its
complications are limited, our recommendations will need
to be evaluated and changed as new information becomes
available.
Patients with Joubert Syndrome and Related Disorders,
in addition to the features mentioned above, have
displayed the following features:
1. Abnormal electroretinogram, indicating co-existent
retinal dysplasia and visual impairment.
2. Optic colobomas, which may also limit vision.
3. Kidney disease, which may include juvenile
nephronophthisis or cystic dysplastic kidneys. In some
patients, the kidney disease has progressed to end-stage
renal failure that required dialysis or transplantation.
4. Liver fibrosis with or without compromised liver
function.
5. Tongue tumors (hamartomas), enlarged tongues,
multiple frenulae or other unusual anomalies of the
mouth.
6. Polydactyly of fingers or toes that may be simple or
complex.
7. Hypothalamic disorders, sometimes related to a
hypothalamic hamartoma.
8. Additional subtle variation in the appearance of
brain structures, including polymicrogyria or
encephalocele.
Because of these findings, we recommend the following
evaluations for patients with Joubert Syndrome and
Related Disorders.
Diagnostic Evaluations (Initial)
1. Careful physical examination to look specifically for
these co-existent features.
2. Pediatric neurological evaluation for careful
assessment of development and cerebellar function.
3. Medical genetics evaluation with attention focused on
genealogy, growth, polydactyly, micro/macrocephaly,
facial dysmorphism, clefts, lingual nodules, genitalia,
and other anomalies.
4. Evaluation of oromotor function by a trained
occupational or speech therapist
5. Brain MRI with axial, coronal, sagittal images
(ideally with 3 mm axial planes through midbrain and
pons) and review of the images by one of the Medical
Advisors of the Joubert Syndrome Foundation.
6. Developmental assessment using the Bayley Scale for
children less than 3 years and specific age-appropriate
motor/speech/language testing for older children.
7. Sleep history with attention to apnea/hyperpnea.
Polysomnogram in all children diagnosed under the age of
1. After the age of 1, this test may be useful if the
child has symptoms of sleep apnea.
8. Baseline pediatric ophthalmologic dilated eye exam to
test for retinal dysplasia and coloboma. If visual
problems are suspected, a visual evoked potential (VEP)
study may be a useful test that does not require
sedation and can be performed as early as 6 months of
age.
9. Baseline electroretinogram (ERG) if possible.
Ideally, this should be done between the ages of 8
months and 3 years, when the sedation required is
minimal.
10. Specific ocular motility examination (with
electrooculogram in older children).
11. Abdominal ultrasound scan with attention to kidneys
and liver.
12. Renal evaluation: Blood urea nitrogen (BUN),
creatinine, complete blood count (CBC), and
first-morning void urinalysis with specific gravity for
concentrating ability. A baseline blood pressure should
be obtained.
13. Liver function tests (LFTs) to include transaminases,
albumin and bilirubin.
14. High resolution karyotype.
15. Referral of the child to one of the Medical Advisors
of the Joubert Syndrome Foundation to discuss results of
testing or for questions.
Annual Evaluations (Yearly)
1. Annual pediatric and neurological evaluation to
monitor systemic or motor abnormalities.
2. Patients may have progressive kidney failure with the
first manifestation being reduced urine concentrating
ability or anemia. Therefore, annual abdominal
ultrasounds, BUN, creatinine, CBC, first-morning void
urinalysis, and blood pressure measurements, are
recommended until at least age 20 years.
3. Ophthalmologic abnormalities may be progressive.
Therefore, annual ophthalmologic evaluation of retina is
recommended with follow-up ERG if indicated by the
ophthalmologist.
4. Annually monitor growth and sexual maturation with
endocrinologic evaluation if indicated
5. Neuropsychological evaluation when patient is able to
cooperate with testing.
6. Periodic developmental assessments as appropriate.
7. Liver evaluation by annual ultrasound (as for
kidneys) and liver function tests.
8. Patients may have problems with swallowing from large
tongues, thus need ongoing evaluation for oromotor
function and symptoms of obstructive apnea.
These are guidelines only. Individual patients may have
unique needs and management may need to be
individualized. If you have any questions about Joubert
Syndrome and Related Disorders, the Joubert Syndrome
Foundation, or other matters, please do not hesitate to
contact one of us.
Sincerely,
Dr. Joseph G. Gleeson
Dr. Melissa A. Parisi
Dr. Bernard L. Maria
Dr. William B. Dobyns
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